Nanopore Mass Spectrometry for Single-Molecule Sequencing

Nanopores are promising tools for DNA sequencing because they can compel a single molecule to translocate the pore in single-file. We seek to couple the processivity of DNA translocation through nanopores with the resolution of mass spectrometry to enable direct, single-molecule sequencing. Electron bombardment or laser irradiation will cause DNA to fragment into its subunits, and the individual DNA bases will be identified by their mass in a train of mass spectral pulses. We will describe the design, assembly, and preliminary testing of a prototype mass spectrometer to test this sequencing concept. Charged particle trajectories were modeled, and the design of extraction optics was optimized so that every DNA subunit could be focused into our mass analyzer. We have also developed a nanopore liquid-to-vacuum interface to serve as the source of single ions.